Unité Mixte de Recherche 216, Institut de Recherche pour le Développement, Mère et Enfant Face aux Infections Tropicales, Université Paris Descartes, Paris, France.
J Infect Dis. 2010 Oct 1;202(7):1095-103. doi: 10.1086/656142.
Theoretical and experimental data support the geographic differentiation strategy as a valuable tool for detecting loci under selection. In the context of Plasmodium falciparum malaria, few populations have been studied, with limited genomic coverage.
We examined geographic differentiation in P. falciparum populations on the basis of 12 single-nucleotide polymorphisms (SNPs) in 4 genes encoding drug resistance determinants, 5 SNPs in 2 genes encoding antigens, and a set of 17 putatively neutral SNPs dispersed on 13 chromosomes. We sampled 326 parasite isolates representing 7 P. falciparum populations from regions with varied levels of malaria transmission (Gabon, Kenya, Madagascar, Mali, Mayotte, Haiti, and the Philippines).
Frequencies of drug resistance alleles varied considerably among populations (mean F(ST), 0.52). In contrast, allele frequencies varied significantly less for antigenic and neutral SNPs (mean F(ST), 0.16 and 0.24, respectively). This contrasting pattern was more pronounced when only the African populations were considered. Signature of selection was detected for most of the resistant SNPs but not for the antigenic SNPs.
These data further validate the utility of geographic differentiation for identifying loci under strong positive selection, such as drug resistance loci. This study also provides frequencies of molecular makers of resistance in some overlooked populations.
理论和实验数据支持地理分化策略作为检测受选择影响的基因座的有用工具。在恶性疟原虫疟疾的背景下，很少有研究对其进行了研究，基因组覆盖范围有限。
我们根据编码耐药决定因素的 4 个基因中的 12 个单核苷酸多态性（SNP）、2 个编码抗原的基因中的 5 个 SNP 以及一组 17 个分散在 13 条染色体上的假定中性 SNP，研究了恶性疟原虫种群的地理分化。我们从疟疾传播程度不同的地区（加蓬、肯尼亚、马达加斯加、马里、马约特岛、海地和菲律宾）采集了代表 7 个恶性疟原虫种群的 326 个寄生虫分离株。
耐药等位基因的频率在不同种群之间差异很大（平均 F（ST）为 0.52）。相比之下，抗原和中性 SNP 的等位基因频率变化较小（平均 F（ST）分别为 0.16 和 0.24）。当仅考虑非洲种群时，这种对比模式更为明显。大多数耐药 SNP 都存在选择的迹象，但抗原 SNP 则不然。
这些数据进一步验证了地理分化在识别受强烈正选择影响的基因座（如耐药基因座）方面的有效性。本研究还提供了一些被忽视的种群中耐药分子标记的频率。
